Phenotypes associated with this allele

• Allele Symbol: Ubr1^tm1Avar
• Allele Name: targeted mutation 1, Alexander Varshavsky
• Allele ID: MGI:2178612
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ubr1^tm1Avar/Ubr1^tm1Avar	either: (involves: 129S/SvEv * 129S1/Sv) or (involves: 129S1/Sv * C57BL/6J)	MGI:2654170
hm2	Ubr1^tm1Avar/Ubr1^tm1Avar	involves: 129S1/Sv * C57BL/6	MGI:3654648
cx3	Ntan1^tm1Avar/Ntan1^tm1Avar Ubr1^tm1Avar/Ubr1^tm1Avar	involves: 129/Sv * C57BL/6	MGI:2654171
cx4	Ubr1^tm1Avar/Ubr1^tm1Avar Ubr2^tm1Ytkw/Ubr2^tm1Ytkw	involves: 129S1/Sv * C57BL/6	MGI:3663588

Genotype
MGI:2654170

hm1

• Allelic Composition: Ubr1^tm1Avar/Ubr1^tm1Avar
• Genetic Background: either: (involves: 129S/SvEv * 129S1/Sv) or (involves: 129S1/Sv * C57BL/6J)

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

adipose tissue

decreased total body fat amount ( J:72859 )

• reduction in amount of adipose tissue

growth/size/body

decreased body weight ( J:72859 )

• lower body mass, with a 20% difference seen at birth, then increased to about 32% for males and about 26% for females at weaning, back to 20% at 4 months and decreased to about 12% at 1 year

homeostasis/metabolism

decreased blood urea nitrogen level ( J:72859 )

hypoglycemia ( J:72859 )

• plasma glucose level is 12% lower than in controls under normal conditions, is 21% lower after a 24-hour fast, and remains unchanged (20%) 24 hours after refeeding

decreased circulating triglyceride level ( J:72859 )

decreased circulating serum albumin level ( J:72859 )

decreased circulating total protein level ( J:72859 )

• levels of total protein in plasma are lower

muscle

decreased skeletal muscle mass ( J:72859 )

• decrease in skeletal muscle mass

behavior/neurological

impaired coordination ( J:72859 )

• exhibit a slightly lower ability to stay on a rotating horizontal rod than controls

Genotype
MGI:3654648

hm2

• Allelic Composition: Ubr1^tm1Avar/Ubr1^tm1Avar
• Genetic Background: involves: 129S1/Sv * C57BL/6

digestive/alimentary system

exocrine pancreatic insufficiency ( J:105229 )

• chymotrypsin and elastase activities are lower in feces, indicating impaired pancreatic exocrine function, however observe no morphological differences in the pancreas

• pancreatic acini are about 100 times less responsive to secretagogue (cholecytoskinin) stimulation, indicating impaired stimulus-secretion coupling in the pancreas

endocrine/exocrine glands

abnormal pancreas physiology ( J:105229 )

• exhibit increased susceptibility to pancreatic injury (induced by cerulein to block secretion and induce acinar cell stress and experimental pancreatitis)

exocrine pancreatic insufficiency ( J:105229 )

• chymotrypsin and elastase activities are lower in feces, indicating impaired pancreatic exocrine function, however observe no morphological differences in the pancreas

• pancreatic acini are about 100 times less responsive to secretagogue (cholecytoskinin) stimulation, indicating impaired stimulus-secretion coupling in the pancreas

behavior/neurological

abnormal learning/memory/conditioning ( J:101662 )

• enhanced non spatial learning

• exhibit superior relearning, though equal first-day retention, on the Lashely III maze

enhanced passive avoidance behavior ( J:105229 )

• perform better in passive avoidance with 92% of mice not re-entering the dark compartment as opposed to 50% of wild-type, but only on the first day of testing, as show similar behavior to wild-type on day 2

abnormal discrimination learning ( J:101662 )

• acquire horizontal-vertical discrimination more quickly

abnormal spatial learning ( J:101662 )

• take longer and swim a greater distance to locate the hidden platform during an 8-week Morris water maze retention, indicating impaired spatial learning

decreased vertical activity ( J:105229 )

decreased locomotor activity ( J:101662 )

• exhibit less spontaneous activity in an open filed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Johanson-Blizzard syndrome		DOID:14694	OMIM:243800	J:105229

Genotype
MGI:2654171

cx3

• Allelic Composition: Ntan1^tm1Avar/Ntan1^tm1Avar; Ubr1^tm1Avar/Ubr1^tm1Avar
• Genetic Background: involves: 129/Sv * C57BL/6

growth/size/body

decreased body weight ( J:72859 )

• weight is lower by about 20%

Genotype
MGI:3663588

cx4

• Allelic Composition: Ubr1^tm1Avar/Ubr1^tm1Avar; Ubr2^tm1Ytkw/Ubr2^tm1Ytkw
• Genetic Background: involves: 129S1/Sv * C57BL/6

Abnormal development of the central nervous system in Ubr1^tm1Avar/Ubr1^tm1Avar Ubr2^tm1Ytkw/Ubr2^tm1Ytkw embryos

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:109036 )

• die by E12.5

growth/size/body

decreased embryo size ( J:109036 )

• embryos are smaller at E10.5 but not at earlier stages

embryo

abnormal vitelline vasculature morphology ( J:109036 )

• by E10.5, blood vessels in the yolk sac are thinner and less branched

embryonic growth arrest ( J:109036 )

• growth ceases at around E10.5

decreased embryo size ( J:109036 )

• embryos are smaller at E10.5 but not at earlier stages

abnormal embryonic neuroepithelium morphology ( J:109036 )

• neuroepithelium at E10.5 is composed of 3 layers (VZ, SVZ, and mantle) instead of two (VZ and mantle) as in wild-type

decreased embryonic neuroepithelium thickness ( J:109036 )

• neuroepithelium at E10.5 is thin, with greater severity in the forebrain than in the spinal cord

• neuroepithelial structures do not increase in thickness after E10.5, in contrast to control embryos

kinked neural tube ( J:109036 )

• neural tubes are normal at E10.5 but by E11.5 become kinked

pale yolk sac ( J:109036 )

• appears pale by E10.5 but not at earlier stages

abnormal vitelline vascular remodeling ( J:109036 )

• staining for Pecam-1 at E10.5 shows that growth, remodeling, and branching of both small and large vessels is impaired

nervous system

increased neural tube apoptosis ( J:109036 )

• exhibit increased amounts apoptosis throughout the neural tubes at E10.5

abnormal neuron differentiation ( J:109036 )

• reduction in proliferation and precocious migration and differentiation of neural progenitor cells

• decrease in the levels of S-phase neural precursor cells throughout the anteroposterior axis at E10.5, indicating impaired proliferation in the ventricular zone (VZ)

• higher numbers of mitotic neural precursors are present in the VZ of the forebrain at E10.5 and the distribution of mitotic cells is disorganized

• many mitotic cells appear to be between the interphase and prophase (instead of prophase or prometaphase as in wild-type), suggesting an arrest

abnormal embryonic neuroepithelium morphology ( J:109036 )

• neuroepithelium at E10.5 is composed of 3 layers (VZ, SVZ, and mantle) instead of two (VZ and mantle) as in wild-type

decreased embryonic neuroepithelium thickness ( J:109036 )

• neuroepithelium at E10.5 is thin, with greater severity in the forebrain than in the spinal cord

• neuroepithelial structures do not increase in thickness after E10.5, in contrast to control embryos

kinked neural tube ( J:109036 )

• neural tubes are normal at E10.5 but by E11.5 become kinked

abnormal forebrain development ( J:109036 )

• by E11.5, forebrain morphology is distorted, with serpentine, thin, often disjointed neuroepithelial layers of varying thickness

cardiovascular system

abnormal blood vessel morphology ( J:109036 )

• larger vessels such as the intracranial artery are thin an poorly developed at E10.5

abnormal vitelline vasculature morphology ( J:109036 )

• by E10.5, blood vessels in the yolk sac are thinner and less branched

abnormal heart morphology ( J:109036 )

• exhibit a large space between the heart and pericardium at E10.5, consistent with the accumulation of pericardial fluid

abnormal myocardial trabeculae morphology ( J:109036 )

• trabeculations are thinner and less abundant

disorganized myocardium ( J:109036 )

• disorganization of the myocardial wall at E10.5

abnormal heart development ( J:109036 )

• development of the atria and ventricles is arrested by E10.5

abnormal heart atrium morphology ( J:109036 )

• development of the atria is arrested by E10.5

abnormal interatrial septum morphology ( J:109036 )

• interatrial septa formation is not observed by E10.5

abnormal heart ventricle morphology ( J:109036 )

• development of the ventricles is arrested by E10.5

• variable levels of ventricular atrophy

abnormal interventricular septum morphology ( J:109036 )

• interventricular septa formation is not observed by E10.5

distended pericardium ( J:109036 )

• seen by E10.5

pericardial effusion ( J:109036 )

• seen by E10.5

hemorrhage ( J:109036 )

• develop local hemorrhages by E10.5 (but not at E9.5)

muscle

abnormal myocardial trabeculae morphology ( J:109036 )

• trabeculations are thinner and less abundant

disorganized myocardium ( J:109036 )

• disorganization of the myocardial wall at E10.5

homeostasis/metabolism

pericardial effusion ( J:109036 )

• seen by E10.5

cellular

increased neural tube apoptosis ( J:109036 )

• exhibit increased amounts apoptosis throughout the neural tubes at E10.5

abnormal neuron differentiation ( J:109036 )

• reduction in proliferation and precocious migration and differentiation of neural progenitor cells

• decrease in the levels of S-phase neural precursor cells throughout the anteroposterior axis at E10.5, indicating impaired proliferation in the ventricular zone (VZ)

• higher numbers of mitotic neural precursors are present in the VZ of the forebrain at E10.5 and the distribution of mitotic cells is disorganized

• many mitotic cells appear to be between the interphase and prophase (instead of prophase or prometaphase as in wild-type), suggesting an arrest